UZH-Logo

The basic residue cluster 55KKWVR59 in CCL5 is required for in vivo biologic function


Segerer, S; Johnson, Z; Rek, A; Baltus, T; von Hundelshausene, P; Kungl, A J; Proudfoot, A E I; Weber, C; Nelson, P J (2009). The basic residue cluster 55KKWVR59 in CCL5 is required for in vivo biologic function. Molecular Immunology, 46(13):2533-2538.

Abstract

Chemokine function in vivo depends on the presentation by structures of the extracellular matrix or on
endothelial surfaces. CCL5 contains two clusters of basic amino acid residues (44RKNR47 and 55KKWVR59)
implicated in presentation of the protein. While 44RKNR47 has been shown to moderate CCL5 binding to
glycosaminoglycans (GAGs), no direct role for the basic residues in the so called 50s loop (55KKWVR59)
as a presentation structure has been published to date. In ex vivo studies both regions were found to be
necessary for direct tissue binding suggesting a role for 55KKWVR59. In vitro T lymphocyte and monocyte
induced firm adhesion under flow, as well as leukocyte recruitment to the peritoneal cavity in vivo was
reduced in the 50s mutant. The binding of the 50s mutant to endothelial cells was significantly reduced
as compared to the wild type protein demonstrated by ELISA. The 50s mutant had little impact on GAG
binding in vitro. These data suggest that functional CCL5 presentation is mediated through both the 40s
as well as the 50s loop with differential functions of the two loops of clusters of basic residues.

Chemokine function in vivo depends on the presentation by structures of the extracellular matrix or on
endothelial surfaces. CCL5 contains two clusters of basic amino acid residues (44RKNR47 and 55KKWVR59)
implicated in presentation of the protein. While 44RKNR47 has been shown to moderate CCL5 binding to
glycosaminoglycans (GAGs), no direct role for the basic residues in the so called 50s loop (55KKWVR59)
as a presentation structure has been published to date. In ex vivo studies both regions were found to be
necessary for direct tissue binding suggesting a role for 55KKWVR59. In vitro T lymphocyte and monocyte
induced firm adhesion under flow, as well as leukocyte recruitment to the peritoneal cavity in vivo was
reduced in the 50s mutant. The binding of the 50s mutant to endothelial cells was significantly reduced
as compared to the wild type protein demonstrated by ELISA. The 50s mutant had little impact on GAG
binding in vitro. These data suggest that functional CCL5 presentation is mediated through both the 40s
as well as the 50s loop with differential functions of the two loops of clusters of basic residues.

Citations

7 citations in Web of Science®
7 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 05 Feb 2010
0 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:August 2009
Deposited On:05 Feb 2010 08:11
Last Modified:05 Apr 2016 13:49
Publisher:Elsevier
ISSN:0161-5890
Publisher DOI:10.1016/j.molimm.2009.05.015
Permanent URL: http://doi.org/10.5167/uzh-28657

Download

[img]
Filetype: PDF - Registered users only
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations